RT Journal Article
SR Electronic
T1 OTX2 Non-Cell Autonomous Activity Regulates Inner Retinal Function
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0012-19.2020
DO 10.1523/ENEURO.0012-19.2020
VO 7
IS 5
A1 Raoul Torero Ibad
A1 Bilal Mazhar
A1 Clémentine Vincent
A1 Clémence Bernard
A1 Julie Dégardin
A1 Manuel Simonutti
A1 Thomas Lamonerie
A1 Ariel A. Di Nardo
A1 Alain Prochiantz
A1 Kenneth L. Moya
YR 2020
UL http://www.eneuro.org/content/7/5/ENEURO.0012-19.2020.abstract
AB OTX2 is a homeoprotein transcription factor expressed in photoreceptors and bipolar cells in the retina. OTX2, like many other homeoproteins, transfers between cells and exerts non-cell autonomous effects such as promoting the survival of retinal ganglion cells that do not express the protein. Here we used a genetic approach to target extracellular OTX2 in the retina by conditional expression of a secreted single-chain anti-OTX2 antibody. Compared with control mice, the expression of this antibody by parvalbumin-expressing neurons in the retina is followed by a reduction in visual acuity in 1-month-old mice with no alteration of the retinal structure or cell type number or aspect. The a-waves and b-waves measured by electroretinogram were also indistinguishable from those of control mice, suggesting no functional deficit of photoreceptors and bipolar cells. Mice expressing the OTX2-neutralizing antibody did show a significant doubling in the flicker amplitude and a reduction in oscillatory potential, consistent with a change in inner retinal function. Our results show that interfering in vivo with OTX2 non-cell autonomous activity in the postnatal retina leads to an alteration in inner retinal cell functions and causes a deficit in visual acuity.